scholarly journals Transglutaminase 6 Is Colocalized and Interacts with Mutant Huntingtin in Huntington Disease Rodent Animal Models

2021 ◽  
Vol 22 (16) ◽  
pp. 8914
Author(s):  
Anja Schulze-Krebs ◽  
Fabio Canneva ◽  
Judith Stemick ◽  
Anne-Christine Plank ◽  
Julia Harrer ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Huntington Disease ◽  
Piriform Cortex ◽  
Transgenic Rat ◽  
Physical Interaction ◽  
Rodent Models ◽  
Mutant Huntingtin ◽  
Calcium Dependent ◽  
Transgenic Rat Model

Mammalian transglutaminases (TGs) catalyze calcium-dependent irreversible posttranslational modifications of proteins and their enzymatic activities contribute to the pathogenesis of several human neurodegenerative diseases. Although different transglutaminases are found in many different tissues, the TG6 isoform is mostly expressed in the CNS. The present study was embarked on/undertaken to investigate expression, distribution and activity of transglutaminases in Huntington disease transgenic rodent models, with a focus on analyzing the involvement of TG6 in the age- and genotype-specific pathological features relating to disease progression in HD transgenic mice and a tgHD transgenic rat model using biochemical, histological and functional assays. Our results demonstrate the physical interaction between TG6 and (mutant) huntingtin by co-immunoprecipitation analysis and the contribution of its enzymatic activity for the total aggregate load in SH-SY5Y cells. In addition, we identify that TG6 expression and activity are especially abundant in the olfactory tubercle and piriform cortex, the regions displaying the highest amount of mHTT aggregates in transgenic rodent models of HD. Furthermore, mHTT aggregates were colocalized within TG6-positive cells. These findings point towards a role of TG6 in disease pathogenesis via mHTT aggregate formation.

Early deficits in olfaction are associated with structural and molecular alterations in the olfactory system of a Huntington disease mouse model

2020 ◽  
Vol 29 (13) ◽  
pp. 2134-2147
Author(s):  
M Laroche ◽  
M Lessard-Beaudoin ◽  
M Garcia-Miralles ◽  
C Kreidy ◽  
E Peachey ◽  
...  
Keyword(s):  
Huntington Disease ◽  
Olfactory System ◽  
Piriform Cortex ◽  
Olfactory Dysfunction ◽  
Altered Expression ◽  
Neuronal Nuclei ◽  
Molecular Alterations ◽  
Cell Death Pathways ◽  
Structural Abnormalities

Abstract Olfactory dysfunction and altered neurogenesis are observed in several neurodegenerative disorders including Huntington disease (HD). These deficits occur early and correlate with a decline in global cognitive performance, depression and structural abnormalities of the olfactory system including the olfactory epithelium, bulb and cortices. However, the role of olfactory system dysfunction in the pathogenesis of HD remains poorly understood and the mechanisms underlying this dysfunction are unknown. We show that deficits in odour identification, discrimination and memory occur in HD individuals. Assessment of the olfactory system in an HD murine model demonstrates structural abnormalities in the olfactory bulb (OB) and piriform cortex, the primary cortical recipient of OB projections. Furthermore, a decrease in piriform neuronal counts and altered expression levels of neuronal nuclei and tyrosine hydroxylase in the OB are observed in the YAC128 HD model. Similar to the human HD condition, olfactory dysfunction is an early phenotype in the YAC128 mice and concurrent with caspase activation in the murine HD OB. These data provide a link between the structural olfactory brain region atrophy and olfactory dysfunction in HD and suggest that cell proliferation and cell death pathways are compromised and may contribute to the olfactory deficits in HD.

Impulsivity trait in the early symptomatic BACHD transgenic rat model of Huntington disease

2016 ◽  
Vol 299 ◽  
pp. 6-10 ◽  
Author(s):  
Giuseppe Manfré ◽  
Valérie Doyère ◽  
Simon Bossi ◽  
Olaf Riess ◽  
Huu Phuc Nguyen ◽  
...  
Keyword(s):  
Rat Model ◽  
Huntington Disease ◽  
Transgenic Rat ◽  
Transgenic Rat Model

P4-048: Role of the genetic background in the neurodegeneration induced by truncated tau in the transgenic rat model

2009 ◽  
Vol 5 (4S_Part_15) ◽  
pp. P445-P445
Author(s):  
Zuzana Stozicka ◽  
Ondrej Bugos ◽  
Miroslava Korenova ◽  
Norbert Zilka ◽  
Jozef Hanes ◽  
...  
Keyword(s):  
Rat Model ◽  
Genetic Background ◽  
Transgenic Rat ◽  
Transgenic Rat Model

scholarly journals 1H NMR based metabolomics of CSF and blood serum: A metabolic profile for a transgenic rat model of Huntington disease

2011 ◽  
Vol 1812 (11) ◽  
pp. 1371-1379 ◽  
Author(s):  
Kim A. Verwaest ◽  
Trung N. Vu ◽  
Kris Laukens ◽  
Laura E. Clemens ◽  
Huu P. Nguyen ◽  
...  
Keyword(s):  
Blood Serum ◽  
1H Nmr ◽  
Rat Model ◽  
Huntington Disease ◽  
Metabolic Profile ◽  
Transgenic Rat ◽  
Transgenic Rat Model

scholarly journals Transfer of disrupted-in-schizophrenia 1 aggregates between neuronal-like cells occurs in tunnelling nanotubes and is promoted by dopamine

Open Biology ◽  
2017 ◽  
Vol 7 (3) ◽  
pp. 160328 ◽  
Author(s):  
Seng Zhu ◽  
Saïda Abounit ◽  
Carsten Korth ◽  
Chiara Zurzolo
Keyword(s):  
Molecular Basis ◽  
Potential Role ◽  
Mental Illnesses ◽  
Transgenic Rat ◽  
Recurrent Depression ◽  
Donor Cells ◽  
Transgenic Rat Model ◽  
Efficient Transfer

The disrupted-in-schizophrenia 1 ( DISC1 ) gene was identified as a genetic risk factor for chronic mental illnesses (CMI) such as schizophrenia, bipolar disorder and severe recurrent depression. Insoluble aggregated DISC1 variants were found in the cingular cortex of sporadic, i.e. non-genetic, CMI patients. This suggests protein pathology as a novel, additional pathogenic mechanism, further corroborated in a recent transgenic rat model presenting DISC1 aggregates. Since the potential role of aggregation of DISC1 in sporadic CMI is unknown, we investigated whether DISC1 undergoes aggregation in cell culture and could spread between neuronal cells in a prion-like manner, as shown for amyloid proteins in neurodegenerative diseases. Co-culture experiments between donor cells forming DISC1 aggregates and acceptor cells showed that 4.5% of acceptor cells contained donor-derived DISC1 aggregates, thus indicating an efficient transfer in vitro . DISC1 aggregates were found inside tunnelling nanotubes (TNTs) and transfer was enhanced by increasing TNT formation and notably by dopamine treatment, which also induces DISC1 aggregation. These data indicate that DISC1 aggregates can propagate between cells similarly to prions, thus providing some molecular basis for the role of protein pathology in CMI.

scholarly journals Modified impact of emotion on temporal discrimination in a transgenic rat model of Huntington disease

2013 ◽  
Vol 7 ◽  
Author(s):  
Alexis Faure ◽  
Mouna Es-seddiqi ◽  
Bruce L. Brown ◽  
Hoa P. Nguyen ◽  
Olaf Riess ◽  
...  
Keyword(s):  
Rat Model ◽  
Huntington Disease ◽  
Temporal Discrimination ◽  
Transgenic Rat ◽  
Transgenic Rat Model

scholarly journals Effects of Human Alpha-Synuclein A53T-A30P Mutations on SVZ and Local Olfactory Bulb Cell Proliferation in a Transgenic Rat Model of Parkinson Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Faustine Lelan ◽  
Cécile Boyer ◽  
Reynald Thinard ◽  
Séverine Rémy ◽  
Claire Usal ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Alpha Synuclein ◽  
Transgenic Rat ◽  
Sprague Dawley ◽  
Motor Impairments ◽  
Resident Cell ◽  
Granular Layers ◽  
Tyrosine Hydroxylase Promoter ◽  
Transgenic Rat Model

A transgenic Sprague Dawley rat bearing the A30P and A53Tα-synuclein (α-syn) human mutations under the control of the tyrosine hydroxylase promoter was generated in order to get a better understanding of the role of the humanα-syn mutations on the neuropathological events involved in the progression of the Parkinson’s disease (PD). This rat displayed olfactory deficits in the absence of motor impairments as observed in most early PD cases. In order to investigate the role of the mutatedα-syn on cell proliferation, we focused on the subventricular zone (SVZ) and the olfactory bulbs (OB) as a change of the proliferation could affect OB function. The effect on OB dopaminergic innervation was investigated. The humanα-syn co-localized in TH-positive OB neurons. No humanα-syn was visualized in the SVZ. A significant increase in resident cell proliferation in the glomerular but not in the granular layers of the OB and in the SVZ was observed. TH innervation was significantly increased within the glomerular layer without an increase in the size of the glomeruli. Our rat could be a good model to investigate the role of human mutatedα-syn on the development of olfactory deficits.

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